On Infinite Time Performance of Nonlinear Model Predictive Controllers

This paper addresses the problem of infinite time performance of model predictive controllers applied to constrained nonlinear systems. The total performance is compared with a finite horizon optimal cost to reveal performance limits of closed-loop model predictive control systems. Based on the Principle of Optimality, an upper and a lower bound of the ratio between the total performance and the finite horizon optimal cost are obtained explicitly expressed by the optimization horizon. The results also illustrate, from viewpoint of performance, how model predictive controllers approaches to infinite optimal controllers as the optimization horizon increases.

Assessing the in vivo efficacy of biologic antiangiogenic therapies

PURPOSE: To review key clinical issues underlying the assessment of in vivo efficacy when using antiangiogenic therapies for cancer treatment.

METHODS: Literature relevant to use of antiangiogenic therapies in cancer was reviewed, with particular emphasis on the assessment of in vivo efficacy of these agents, as well as additional angiogenic factors that could play a role in escape from angiogenesis inhibition.

RESULTS: In order to grow and metastasize, tumors need to continually acquire new blood supplies; therefore, therapeutic inhibition of angiogenesis has become a component of anticancer treatment for many tumor types. Bevacizumab, a humanized monoclonal antibody directed at vascular endothelial growth factor A (VEGF-A), has shown activity in combination with chemotherapy in metastatic colorectal cancer. Nevertheless, the use of antiangiogenic therapies remains suboptimal; specifically, optimal dose, duration of therapy, and combination of agents remain unknown. Also, at present, it is not possible to determine which patients are most likely to respond to a given form of antiangiogenic therapy. There has been increased recognition of alternative pathways possibly associated with disease progression in patients undergoing antiangiogenic therapy targeted at VEGF-A. Multiligand-targeted antiangiogenic therapies, such as ziv-aflibercept (formerly known as aflibercept, VEGF Trap), are currently undergoing clinical evaluation. Ziv-aflibercept forms monomeric complexes with VEGF-A, VEGF-B, and PlGF, which have a long half-life, allowing optimization of ziv-aflibercept doses and angiogenic blockage.

CONCLUSIONS: Although antiangiogenic therapies have increased treatment options for cancer patients, their use is limited by a lack of established and standardized methodology to evaluate their efficacy in vivo. Circulating endothelial cells, hypertension, and several molecular and imaging-based markers have potential for use as biomarkers in these patients and may better define appropriate patient populations.

Scotland’s Curriculum for Excellence: a defence of autonomy and personhood.

Curriculum for Excellence, Scotland’s 3-18 curriculum, has been described as ‘the most significant curricular change in Scotland for a generation’ (McAra, Broadley and McLauchlan, 2013:223). The purpose of the curriculum is ‘encapsulated’ in four capacities in order that learners become i) successful learners, ii) confident individuals, iii) responsible citizens, and iv) effective contributors. With particular reference to these capacities, we explore the principle of autonomy as it pertains to both individual and collective flourishing seeking to disarm commonplace criticisms of autonomy by arguing that it might be put to work in CfE as a potentially multi-dimensional, context-sensitive concept that is relational as well as individual. We conclude that the four capacities lend themselves to re-consideration and re-mapping in pursuit of autonomy and flourishing premised on the principles of liberal personhood.

Recognising difference while promoting cohesion: the role of collaborative networks in education

The chapter outlines various approaches taken to the challenge of divided societies through education systems and links this to debates on political approaches to conflict resolution in Northern Ireland. The education debate has structural and affective components, while the political debate revolves around the privileging of identity or commonality. Applying the principle of recognition and the importance of tolerance is seen to provide a range of policy options, but the evidence of education interventions in Northern Ireland does not highlight any one policy option as the most effective, nor did the end of the violent conflict produce a new consensus on a way forward. The chapter argues that a key additional element to effective practice might be provided through the promotion of shared education through collaborative networks of schools which allows for the continued operation of separate schools while promoting an integrated experience for pupils and teachers.

Development of a potent and selective cell penetrant Legumain inhibitor

This Letter describes the continued SAR exploration of small molecule Legumain inhibitors with the aim of developing a potent and selective in vitro tool compound. Work continued in this Letter explores the use of alternative P2-P3 linker units and the P3 group SAR which led to the identification of 10t, a potent, selective and cellularly active Legumain inhibitor. We also demonstrate that 10t has activity in both cancer cell viability and colony formation assays.

Effect of technique on intraocular pressure after combined cataract and glaucoma surgery: An evidence-based review.

TOPIC:

To analyze the literature pertaining to the techniques used in combined cataract and glaucoma surgery, including the technique of cataract extraction, the timing of the surgery (staged procedure versus combined procedure), the anatomic location of the operation, and the use of antifibrosis agents.

CLINICAL RELEVANCE:

Cataract and glaucoma are both common conditions and are often present in the same patient. There is no agreement concerning the optimal surgical management of these disorders when they coexist.

METHODS/LITERATURE REVIEWED:

Electronic searches of English language articles published since 1964 were conducted in Pub MED and CENTRAL, the Cochrane Collaboration's database. These were augmented by a hand search of six ophthalmology journals and the reference lists of a sample of studies included in the literature review. Evidence grades (A, strong; B, moderate; C, weak; I, insufficient) were assigned to the evidence that involved a direct comparison of alternative techniques.

RESULTS:

The preponderance of evidence from the literature suggests a small (2-4 mmHg) benefit from the use of mitomycin-C (MMC), but not 5-fluorouracil (5-FU), in combined cataract and glaucoma surgery (evidence grade B). Two-site surgery provides slightly lower (1-3 mmHg) intraocular pressure (IOP) than one-site surgery (evidence grade C), and IOP is lowered more (1-3 mmHg) by phacoemulsification than by nuclear expression in combined procedures (evidence grade C). There is insufficient evidence to conclude either that staged or combined procedures give better results or that alternative glaucoma procedures are superior to trabeculectomy in combined procedures.

CONCLUSIONS:

In the literature on surgical techniques and adjuvants used in the management of coexisting cataract and glaucoma, the strongest evidence of efficacy exists for using MMC, separating the incisions for cataract and glaucoma surgery, and removing the nucleus by phacoemulsification.

A Molecular Mechanism for Sequential Activation of a G Protein-Coupled Receptor

Ligands targeting G protein-coupled receptors (GPCRs) are currently classified as either orthosteric, allosteric, or dualsteric/bitopic. Here, we introduce a new pharmacological concept for GPCR functional modulation: sequential receptor activation. A hallmark feature of this is a stepwise ligand binding mode with transient activation of a first receptor site followed by sustained activation of a second topographically distinct site. We identify 4-CMTB (2-(4-chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide), previously classified as a pure allosteric agonist of the free fatty acid receptor 2, as the first sequential activator and corroborate its two-step activation in living cells by tracking integrated responses with innovative label-free biosensors that visualize multiple signaling inputs in real time. We validate this unique pharmacology with traditional cellular readouts, including mutational and pharmacological perturbations along with computational methods, and propose a kinetic model applicable to the analysis of sequential receptor activation. We envision this form of dynamic agonism as a common principle of nature to spatiotemporally encode cellular information.

Experimental Study on Channel Reciprocity in Wireless Key Generation

Key generation from wireless channels is a promising alternative to public key cryptography for the establishment of cryptographic keys. It is the first paper to experimentally study the channel reciprocity principle of key generation, through investigating and quantifying channel measurements' cross-correlation relationship affected by noise and non-simultaneous measurements. Channel measurements, both received signal strength and channel state information, are collected from a real experimental platform using the wireless open access research platform (WARP) in a multipath office room. We found that in a slow fading channel (e.g., with a coherence time of about 50~ms), the channel cross-correlation is impacted greatly by noise but little by non-simultaneous measurements with a small sampling time difference (e.g., 0.06 ms). The resolution of the sampling time difference can be satisfied by wireless systems such as IEEE 802.11 to maintain an acceptable cross-correlation coefficient without affecting the bandwidth and communication efficiency.